title: Implantation of ultrathin, biofunctionalized polyimide membranes into the subretinal space of rats.
abstract: Subretinal implants aim to replace the photoreceptor function in patients suffering from degenerative retinal disease by topically applying electrical stimuli in the subretinal space. Critical obstacles in the design of high-resolution subretinal implants include the proximity of stimulating electrodes to the target cells and enabling nutrient flow between the retina and the choroid. The present work evaluates the adhesion, migration and survival of retinal cells on an ultrathin (5 μm), highly porous (Ø 1 μm spaced 3 μm), gelatin-coated polyimide (PI) membrane. The biocompatibility was examined in mice indicating a good tolerance upon subcutaneous implantation with only a mild inflammatory response. In addition, organotypic cultures of rat retina evidenced that the porous membrane allowed the necessary nutrient flow for the retinal cell survival and maintenance. A transscleral implantation technique was applied to position the membrane into the subretinal space of rats. The effect on the obtained retinal integration was investigated in vivo using scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). In 12 out of 18 rat eyes, the implant was successfully placed subretinally. SLO and OCT demonstrated complete retinal attachment and fluorescein angiography showed no retinal vascular abnormalities over and around the implant, immediately after and up to four weeks after the implantation. Histological examination of the eyes showed a close attachment of a thin fibrocyte layer to the implant, the occlusion of the pores by living cells and the survival of some photoreceptors at the implantation site.
authors.affiliation: Section for Experimental Vitreoretinal Surgery, Centre for Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany. Sylvie.Julien@med.uni-tuebingen.de
authors.forename: Sylvie
authors.initials: S
authors.lastname: Julien
authors.forename: Tobias
authors.initials: T
authors.lastname: Peters
authors.forename: Focke
authors.initials: F
authors.lastname: Ziemssen
authors.forename: Blanca
authors.initials: B
authors.lastname: Arango-Gonzalez
authors.forename: Susanne
authors.initials: S
authors.lastname: Beck
authors.forename: Hagen
authors.initials: H
authors.lastname: Thielecke
authors.forename: Heiko
authors.initials: H
authors.lastname: Büth
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Vlierberghe
authors.forename: Milada
authors.initials: M
authors.lastname: Sirova
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossmann
authors.forename: Blanka
authors.initials: B
authors.lastname: Rihova
authors.forename: Etienne
authors.initials: E
authors.lastname: Schacht
authors.forename: Peter
authors.initials: P
authors.lastname: Dubruel
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002470:Cell Survival; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009924:Organ Culture Techniques; D019919:Prosthesis Implantation / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000601:surgery* / Q000648:ultrastructure; D041623:Tomography, Optical Coherence
chemical_list: D008567:Membranes, Artificial